In the continuation of the grant we propose to continue studies of the effects of ethanol and acetaldehyde in vitro, and of chronic ethanol intoxication, on subcellular constituents of skeletal and cardiac muscle. These studies include ion flux across the cell membranes of cultured myocytes, calcium transport by sarcoplasmic reticulum, membrane structure of mitochondria and the interaction of calcium and the contractile proteins. Preparative methods will include fractionation of cells, isolation of mitochondria and sarcoplasmic reticulum, tissue culture of beating myocytes, and purification of the components of the contractile proteins. Chronic models will include rats, dogs and guinea pigs, the first two being well defined, and the last a newly developed model. An understanding of injury at the subcellular level should help in the elucidation of the pathogenesis of alcohol-induced reversible acute functional changes, and irreversible chronic alterations of alcoholic cardiomyopathy and myopathy.